Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and meta‐analysis
Top Cited Papers
Open Access
- 29 January 2019
- journal article
- review article
- Published by Wiley in Diabetes, Obesity and Metabolism
- Vol. 21 (5), 1237-1250
- https://doi.org/10.1111/dom.13648
Abstract
Aim The use of sodium glucose co‐transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has been limited, primarily because glycemic efficacy is dependent on kidney function. We performed a systematic review and meta‐analysis to assess the efficacy and safety of SGLT2 inhibitors in patients with T2DM and CKD, defined as estimated glomerular filtration rate (eGFR) 2. Materials and methods We searched MEDLINE, EMBASE and the Cochrane Library to August 7, 2018, as well as the websites of the United States, European, and Japanese regulatory authorities to July 27, 2018 for data from randomized controlled trials of SGLT2 inhibitors that included reporting of effects on biomarkers, cardiovascular, renal, or safety outcomes in individuals with T2DM and CKD. Random effects models and inverse variance weighting were used to calculate relative risks with 95% confidence intervals. Results Data were obtained from 27 studies with up to 7,363 participants contributing. In patients with T2DM and CKD, SGLT2 inhibitors lowered glycated hemoglobin (–0.29%, 95% CI –0.39 to –0.19), as well as blood pressure, body weight, and albuminuria. SGLT2 inhibition reduced the risk of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (RR 0.81, 95% CI 0.70‐0.94) and heart failure (RR 0.61, 95% CI 0.48‐0.78), without a clear effect on all‐cause mortality (HR 0.86, 95% CI 0.73‐1.01). These agents also attenuated the annual decline in eGFR slope (placebo‐subtracted difference of 1.35 mL/1.73m2/year, 95% CI 0.78‐1.93) and reduced the risk of the composite renal outcome (HR 0.71, 95% CI 0.53‐0.95). There was no evidence of additional risks with SGLT2 inhibition in CKD beyond those already known for the class, although heterogeneity was observed across individual agents for some safety outcomes. Conclusion Currently available data suggest that despite only modest reductions in glycated hemoglobin, SGLT2 inhibitors reduce the risk of cardiovascular and renal outcomes in patients with T2DM and CKD, without clear evidence of additional safety concerns.Keywords
Funding Information
- National Health and Medical Research Council of Australia
This publication has 103 references indexed in Scilit:
- Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney diseaseDiabetes, Obesity and Metabolism, 2013
- Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exerciseDiabetes, Obesity and Metabolism, 2013
- Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trialInternational Journal of Clinical Practice, 2012
- The Cochrane Collaboration's tool for assessing risk of bias in randomised trialsBMJ, 2011
- Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trialDiabetes, Obesity and Metabolism, 2011
- Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trialThe Lancet, 2010
- Dapagliflozin Monotherapy in Type 2 Diabetic Patients With Inadequate Glycemic Control by Diet and ExerciseDiabetes Care, 2010
- Glucose Control and Vascular Complications in Veterans with Type 2 DiabetesThe New England Journal of Medicine, 2009
- Sodium-Glucose Cotransport Inhibition With Dapagliflozin in Type 2 DiabetesDiabetes Care, 2008
- Effects of Intensive Glucose Lowering in Type 2 DiabetesThe New England Journal of Medicine, 2008